452 Letters in Organic Chemistry, 2010, Vol. 7, No. 6
Zhou et al.
OCOOBn
BnOOCO
O
OCOOBn
BnOOCO
O
Boc
Ph
NH
O
a
O
O
O
HO
OH
OAc
O
OH
OAc
OBz
OBz
O
Ph
O
Boc
N
8
6a
OH
HO
O
O
Boc
10
O
NH
O
c
b
O
1
Ph
O
OH
OAc
O
OBz
O
9
Scheme 1. Semi-synthesis of Docetaxel.
Reagents and conditions: (a) 10, NaH, NaN(TMS)2, -40 oC, THF, 2.5h, 80%; (b) Pd/C, H2, THF, r.t., 5h, 98%; (c) AcOH/H2O(4:1, v/v), r.t.,
4h, 78%.
benefit from the easy handle, high yield and the high
purity[8] of docetaxel.
REFERENCES
[1]
[2]
[3]
Lyseng-Williamson, K. A.; Fenton, C. Docetaxel: a review of its
use in metastatic breast cancer. Drugs, 2005, 65, 2513.
Clarke, S. J.; Rivory, L. P. Clinical pharmacokinetics of docetaxel.
Chin. Pharmacokinet., 1999, 36, 99.
Chauviere, G.; Guenard, D.; Picot, F.; Senilh, V.; Potier, P. Isoln
from Taxus baccala L. and in vitro inhibition of depolymerization
of microtubules into tubulin. C. R. Acad. Sci. Paris, II, 1981, 293,
501.
EXPERIMENTAL SECTION
C-7, C-10-dibenzyloxycarbonyl-10-Deacetyl baccatin III
(6a)
10-DAB III (15g, 28mmol) and DMAP (3.4g, 28mmol)
were dissolved in anhydrous THF (150 mL) and the solution
was warmed to 40 C. Benzyl chloromate (0.37 mol/L in
[4]
[5]
[6]
Appendino, G.; Belloro, E.; Jakupovic, S.; Danieli, B,; Jakupovic,
J.; Bombardelli, E. Synthesis of paclitaxel (docetaxel)
/ 2-
o
deacetoxytaxinine J dimers. Tetrahedron, 1999, 55, 6567.
Guéritte-Voegelein, F.; Sénilh, V.; David, D.; Guénard, P. P.
Chemical studies of 10-deacetyl baccatin III : Hemisynthesis of
taxol derivatives. Tetrahedron, 1986, 42, 4451.
Heo, J. H.; Park, S. J.; Kang, J. H.; Lee, I. S.; Lee, J. S.; Park, Y. J.;
Kim, K. S.; Lee, J. Y. Development of New Efficient Synthetic
Methods for Docetaxel. Bull. Korean. Chem. Soc., 2009, 30, 25,
and the references therein.
Sisti, N. J.; Swindell, C. S.; Chander, M. C. Intermediate for use in
docetaxel synthesis and production method therefor. U.S. Patent, 6,
107, 497, 2000.
The purity of docetaxel synthesized by our method was 99.6%
which was determined by HPLC. (YMC C18(150ꢁ46mm,5μm),
Methanol/Acetonitrile/H2O = 33/25/42, flow rate 1.5 mL/min,
detection at 232 nm, tR 14.8 min).
THF, 150 mL) was added dropwise over 1h, and the solution
o
was warmed to 60 C, and stirred for an additional 30 min.
The mixture was then cooled to r.t., filtrated, and washed
with THF. The combined filtrate was concentrated under
reduced pressure, and the crude product was purified by
column chromatography to obtain pure 6a as a white solid
(18g, 81%). 13C NMR (125 MHz, CDCl3) ꢀ 10.6, 15.4, 20.1,
22.6, 25.6, 26.6, 33.4, 38.4, 42.7, 47.4, 56.3, 68.0, 68.0, 69.9,
70.1, 74.3, 75.6, 76.4, 78.7, 79.0, 80.6, 83.9, 128.3, 128.3,
128.4, 128.44, 128.5, 128.6, 128.7, 129.3, 130.1, 131.5,
133.7, 135.2, 135.3, 145.6, 154.2, 154.2, 167.0, 170.7, 202.0;
ESI-MS calcd. for C45H48O14Na [M+Na]+: 835.3, found
835.6.
[7]
[8]
ACKNOWLEDGEMENT
We appreciate the financial support from the National
Natural Science Foundation of China (No. 20902114).